The proposed research is a continuation and extension of ongoing developmental studies of the hepatic mixed-function oxidase system. The major thrust of our program is toward elucidation of relationships between this system and steroid metabolism, focusing on possible inhibitory effects of progesterone or a metabolite, such as pregnanolone, during pregnancy and the neonatal period. Attention will be given to the inhibition of bilirubin conjugation by progesterone metabolites. Another aspect of the proposal deals with the postulate that alterations in rate or pathway of the hepatic metabolism of steroids may play an important role in regulation of their biologic effects. Many studies have indicated the similarities of microsomal enzymes responsible for oxidative drug metabolism and steroid hydroxylation reactions. These microsomal systems are influenced by a variety of genetic, hormonal, ontogenetic, nutritional and environmental factors. Our studies will explore the age and hormonal influences, and the effects of administration of drugs such as phenobarbital, which are known to increase enzymic activity for biotransformation of drugs and steroids and cause proliferation of the smooth endoplasmic reticulum. The long-term goals are to increase knowledge in the areas of reproductive physiology, developmental pharmacology, and therapeutics by delineating the complex interrelationships between hepatic drug and steroid metabolism and the physiologic and pharmacologic activities of these agents.